Recently many extracts and their derivatives oriented from natural plants, such as vincristine, vinbalstine, camptothecin, taxol and its derivatives, palitaxel and docetaxel, have been widely used in clinical chemical therapy of a malignant tumor. Therefore, the effect of the extracts from natural plants has been a burgeoning research in the field of new drug development.
According to present publication, protoapegenone is a compound derived from Thelypteris torresiana produced in Taiwan. The compound has strong cytotoxic activities to many human cancer cell lines, including breast cancer cells (MCF-7, MDA-MB-231), liver cancer cells (Hep G2, and Hep 3B), and lung cancer cells (A549). (Planta Medica 71:867-870, 2005)
Prior to that, the protoapigenone can be obtained merely by extraction and isolation from natural plants. However, the efficiency of collecting the compound is under influence of unstable sources such as plant genes, humidity, and latitude, altitude of the collection location, season and individual variation of the plants.
In view of the above, the inventors develop a method for producing a compound for treating cancer cells through total synthesis or semi-synthesis based on the inventors' experience in studying the ingredient of natural plants and chemical synthesis for a long time. By using such preparation, the protoapigenone can be produced from commercially available chemical products without extracting from natural plants. Moreover, the activity of the synthetic compound has no obvious difference with nature product through a comparison of activity. Moreover, the source of the compound would be stable and preparation time would be saved. Further, yield of the compound can be estimated in a large scale production by using the synthetic method of the present invention.
Besides, many derivatives of protoapigenone will be produced from different initiators, reagents and intermediator. Moreover, the acidity, the alkalinity, the lipid solubility, the solubility, the activity and the toxicity of the compound can be changed by substituting with different functional groups so that a more potent compound with cytotoxic effect can be afforded. The summary of the present invention is described below.